Allergen-enhanced thrombomodulin (blood dendritic cell antigen 3, CD141) expression on dendritic cells is associated with a TH2-skewed immune response.
BACKGROUND
Dendritic cells (DCs) are important in allergic diseases such as asthma, although little is known regarding the mechanisms by which DCs induce T(H)2-polarized responses in atopic individuals. It has been suggested that intrinsic properties of allergens can directly stimulate T(H)2 polarizing functions of DCs, but little is known of the underlying mechanisms.


OBJECTIVE
To identify novel genes expressed by house dust mite (HDM) allergen-exposed DCs.


METHODS
We screened for allergen-induced gene expression by microarray, and validated differentially expressed genes at the mRNA and protein levels.


RESULTS
Thrombomodulin (CD141, blood dendritic cell antigen 3) expression by microarray was higher on HDM-stimulated DCs from atopic (relative to nonatopic) individuals. These findings were confirmed at both the mRNA and protein levels in an independent group. Purified thrombomodulin(+) DCs induced a strongly T(H)2-polarized cytokine response by allergen-specific T cells compared with DCs lacking thrombomodulin. In vivo, thrombomodulin(+) circulating DCs were significantly more frequent in subjects with HDM allergy and asthma, compared with control subjects. Furthermore, thrombomodulin expression in blood leukocytes was higher in children with acute asthma than at convalescence 6 weeks later.


CONCLUSIONS
Thrombomodulin expression on DCs may be involved in the pathogenesis of atopy and asthma.
Yerkovich
Stephanie T
ST
Telethon Institute for Child Health Research, Centre for Child Health Research, Faculty of Medicine and Dentistry, University of Western Australia, Perth, Australia.
Roponen
Marjut
M
Smith
Miranda E
ME
McKenna
Kathy
K
Bosco
Anthony
A
Subrata
Lily S
LS
Mamessier
Emilie
E
Wikström
Matthew E
ME
Le Souef
Peter
P
Sly
Peter D
PD
Holt
Patrick G
PG
Upham
John W
JW
D000293:Adolescent; D000328:Adult; D000368:Aged; D039741:Antigens, Dermatophagoides / Q000276:immunology* / Q000494:pharmacology; D000954:Antigens, Surface / Q000096:biosynthesis / Q000276:immunology*; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003289:Convalescence; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology; D018180:Thrombomodulin / Q000096:biosynthesis / Q000276:immunology*
D039741:Antigens, Dermatophagoides; D000954:Antigens, Surface; C546931:THBD protein, human; D018180:Thrombomodulin